tbuckley/cabot-search huggingface dataset:
Pediatric Psychiatric Emergency Services—Stasis in Crisis
Authors: Jennifer F. Havens, Mollie C. Marr
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Restoration of Cardiac Myosin Light Chain Kinase Ameliorates Systolic Dysfunction by Reducing Superrelaxed Myosin
Authors: Tatsuro Hitsumoto, Osamu Tsukamoto, Ken Matsuoka, Junjun Li, Li Liu, Yuki Kuramoto, Shuichiro Higo, Shou Ogawa, Noboru Fujino, Shohei Yoshida, Hidetaka Kioka, Hisakazu Kato, Hideyuki Hakui, Yuki Saito, Chisato Okamoto, Hijiri Inoue, Jo Hyejin, Kyoko Ueda, Takatsugu Segawa, Shunsuke Nishimura, Yoshihiro Asano, Hiroshi Asanuma, Akiyoshi Tani, Riyo Imamura, Shinsuke Komagawa, Toshio Kanai, Masayuki Takamura, Yasushi Sakata, Masafumi Kitakaze, Jun-ichi Haruta, Seiji Takashima
Journal: Circulation (2023)

Cardiac-specific myosin light chain kinase (cMLCK), encoded by
Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma: Final Analysis of KEYNOTE-170
Authors: Pier Luigi Zinzani, Catherine Thieblemont, Vladimir Melnichenko, Krimo Bouabdallah, Jan Walewski, Alejandro Majlis, Laura Maria Fogliatto, Alejandro Martin Garcia-Sancho, Beth Christian, Zafer Gulbas, Muhit Özcan, Guilherme Fleury Perini, Herve Ghesquieres, Margaret A. Shipp, Seth Thompson, Samhita Chakraborty, Patricia Marinello, Philippe Armand
Journal: Blood (2023)

Previous analyses of the phase 2 KEYNOTE-170 (NCT02576990) study demonstrated effective antitumor activity and acceptable safety of pembrolizumab 200 mg given every 3 weeks for up to 35 cycles (~2 years) in patients with relapsed/refractory (R/R) primary mediastinal B-cell lymphoma (PMBCL) whose disease progressed after or who were ineligible for autologous stem cell transplantation. End points included objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR) by investigator per 2007 Response Criteria; overall survival (OS); and safety. In this final analysis, median duration of follow-up was 48.7 months (range, 41.2-56.2). ORR was 41.5% (complete response, 20.8%; partial response, 20.8%). Median DOR was not reached; no patients who achieved complete response had progressed at the data cutoff. Median PFS was 4.3 months; 4-year PFS rate was 33.0%. Median OS was 22.3 months; 4-year OS rate was 45.3%. At the data cutoff, 30 patients (56.6%) had any-grade treatment-related adverse events (AEs); the most common were neutropenia, asthenia, and hypothyroidism. Grade 3 or 4 treatment-related AEs occurred in 22.6% of patients; no grade 5 AEs occurred. After 4 years of follow-up, pembrolizumab continued to provide durable responses, with promising trends for long-term survival and acceptable safety in R/R PMBCL.
Screening for Latent Tuberculosis Infection in Adults
Authors: Carol M. Mangione, Michael J. Barry, Wanda K. Nicholson, Michael Cabana, David Chelmow, Tumaini Rucker Coker, Esa M. Davis, Katrina E. Donahue, Carlos Roberto Jaén, Li Li, Gbenga Ogedegbe, Goutham Rao, John M. Ruiz, James Stevermer, Sandra Millon Underwood, John B. Wong
Journal: JAMA (2023)

Importance In the US, tuberculosis remains an important preventable disease, including active tuberculosis, which may be infectious, and latent tuberculosis infection (LTBI), which is asymptomatic and not infectious but can later progress to active disease. The precise prevalence rate of LTBI in the US is difficult to determine; however, estimated prevalence is about 5.0%, or up to 13 million persons. Incidence of tuberculosis varies by geography and living accommodations, suggesting an association with social determinants of health. Objective To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on LTBI screening and treatment in asymptomatic adults seen in primary care, as well as the accuracy of LTBI screening tests. Population Asymptomatic adults 18 years or older at increased risk for tuberculosis. Evidence Assessment The USPSTF concludes with moderate certainty that there is a moderate net benefit in preventing active tuberculosis disease by screening for LTBI in persons at increased risk for tuberculosis infection. Recommendation The USPSTF recommends screening for LTBI in populations at increased risk. (B recommendation)
Breaking bad
Authors: Mohini Bhattacharya, Alexander R. Horswill
Journal: The Journal of Experimental Medicine (2023)

DNASE1 (D1) and DNASE1L3 (D1L3) synergistically reduce the severity of systemic infections caused by Staphylococcus aureus. In this issue of JEM, Lacey et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20221086) develop D1−/−, D1L3−/−, and D1−/−D1L3−/− mice to show that exogenous addition of the DNase formulation Dornase alfa can facilitate removal of biofilms.
β-Catenin–Driven Differentiation Is a Tissue-Specific Epigenetic Vulnerability in Adrenal Cancer
Authors: Dipika R. Mohan, Kleiton S. Borges, Isabella Finco, Christopher R. LaPensee, Juilee Rege, April L. Solon, Donald W. Little, Tobias Else, Madson Q. Almeida, Derek Dang, James Haggerty-Skeans, April A. Apfelbaum, Michelle Vinco, Alda Wakamatsu, Beatriz M.P. Mariani, Larissa Costa Amorim, Ana Claudia Latronico, Berenice B. Mendonca, Maria Claudia N. Zerbini, Elizabeth R. Lawlor, Ryoma Ohi, Richard J. Auchus, William E. Rainey, Suely K.N. Marie, Thomas J. Giordano, Sriram Venneti, Maria Candida Barisson Villares Fragoso, David T. Breault, Antonio Marcondes Lerario, Gary D. Hammer
Journal: Cancer Research (2023)

Adrenocortical carcinoma (ACC) is a rare cancer in which tissue-specific differentiation is paradoxically associated with dismal outcomes. The differentiated ACC subtype CIMP-high is prevalent, incurable, and routinely fatal. CIMP-high ACC possess abnormal DNA methylation and frequent β-catenin-activating mutations. Here, we demonstrated that ACC differentiation is maintained by a balance between nuclear, tissue-specific β-catenin-containing complexes, and the epigenome. On chromatin, β-catenin bound master adrenal transcription factor SF1 and hijacked the adrenocortical super-enhancer landscape to maintain differentiation in CIMP-high ACC; off chromatin, β-catenin bound histone methyltransferase EZH2. SF1/β-catenin and EZH2/β-catenin complexes present in normal adrenals persisted through all phases of ACC evolution. Pharmacologic EZH2 inhibition in CIMP-high ACC expelled SF1/β-catenin from chromatin and favored EZH2/β-catenin assembly, erasing differentiation and restraining cancer growth in vitro and in vivo. These studies illustrate how tissue-specific programs shape oncogene selection, surreptitiously encoding targetable therapeutic vulnerabilities.
National Trends in Mental Health–Related Emergency Department Visits Among Youth, 2011-2020
Authors: Tanner J. Bommersbach, Alastair J. McKean, Mark Olfson, Taeho Greg Rhee
Journal: JAMA (2023)

There has been increasing concern about the burden of mental health problems among youth, especially since the COVID-19 pandemic. Trends in mental health-related emergency department (ED) visits are an important indicator of unmet outpatient mental health needs.To estimate annual trends in mental health-related ED visits among US children, adolescents, and young adults between 2011 and 2020.Data from 2011 to 2020 in the National Hospital Ambulatory Medical Care Survey, an annual cross-sectional national probability sample survey of EDs, was used to examine mental health-related visits for youths aged 6 to 24 years (unweighted = 49 515).Mental health-related ED visits included visits associated with psychiatric or substance use disorders and were identified by International Classification of Diseases-Ninth Revision, Clinical Modification (ICD-9-CM; 2011-2015) and ICD-10-CM (2016-2020) discharge diagnosis codes or by reason-for-visit (RFV) codes. We estimated the annual proportion of mental health-related pediatric ED visits from 2011 to 2020. Subgroup analyses were performed by demographics and broad psychiatric diagnoses. Multivariable-adjusted logistic regression analyses estimated factors independently associated with mental health-related ED visits controlling for period effects.From 2011 to 2020, the weighted number of pediatric mental health-related visits increased from 4.8 million (7.7% of all pediatric ED visits) to 7.5 million (13.1% of all ED visits) with an average annual percent change of 8.0% (95% CI, 6.1%-10.1%; P < .001). Significant linearly increasing trends were seen among children, adolescents, and young adults, with the greatest increase among adolescents and across sex and race and ethnicity. While all types of mental health-related visits significantly increased, suicide-related visits demonstrated the greatest increase from 0.9% to 4.2% of all pediatric ED visits (average annual percent change, 23.1% [95% CI, 19.0%-27.5%]; P < .001).Over the last 10 years, the proportion of pediatric ED visits for mental health reasons has approximately doubled, including a 5-fold increase in suicide-related visits. These findings underscore an urgent need to improve crisis and emergency mental health service capacity for young people, especially for children experiencing suicidal symptoms.
Monitoring Sarcoma Response to Immune Checkpoint Inhibition and Local Cryotherapy with Circulating Tumor DNA Analysis
Authors: Nam Q. Bui, Neda Nemat-Gorgani, Ajay Subramanian, Ileana A. Torres, Marta Lohman, Timothy J. Sears, Matt van de Rijn, Gregory W. Charville, Hans-Christoph Becker, David S. Wang, Gloria L. Hwang, Kristen N. Ganjoo, Everett J. Moding
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Immune checkpoint inhibition has led to promising responses in soft tissue sarcomas (STS), but the majority of patients do not respond and biomarkers of response will be crucial. Local ablative therapies may augment systemic responses to immunotherapy. We evaluated circulating tumor DNA (ctDNA) as a biomarker of response in patients treated on a trial combining immunotherapy with local cryotherapy for advanced STS. Patients and Methods: We enrolled 30 patients with unresectable or metastatic STS to a phase II clinical trial. Patients received ipilimumab and nivolumab for four doses followed by nivolumab alone with cryoablation performed between cycles 1 and 2. The primary endpoint was objective response rate (ORR) by 14 weeks. Personalized ctDNA analysis using bespoke panels was performed on blood samples collected prior to each immunotherapy cycle. Results: ctDNA was detected in at least one sample for 96% of patients. Pretreatment ctDNA allele fraction was negatively associated with treatment response, progression-free survival (PFS), and overall survival (OS). ctDNA increased in 90% of patients from pretreatment to postcryotherapy, and patients with a subsequent decrease in ctDNA or undetectable ctDNA after cryotherapy had significantly better PFS. Of the 27 evaluable patients, the ORR was 4% by RECIST and 11% by irRECIST. Median PFS and OS were 2.7 and 12.0 months, respectively. No new safety signals were observed. Conclusions: ctDNA represents a promising biomarker for monitoring response to treatment in patients with advanced STS, warranting future prospective studies. Combining cryotherapy and immune checkpoint inhibitors did not increase the response rate of STS to immunotherapy.
Longitudinal Outcomes of Cumulative Impact Exposure on Oculomotor Functioning in Professional Motorsport Drivers
Authors: Danielle M. Ransom, Luis M. Ahumada, P. Patrick Mularoni, Terry R. Trammell, Geoff L. Billows
Journal: JAMA Network Open (2023)

Professional motorsport drivers are regularly exposed to biomechanical forces comparable with those experienced by contact and collision sport athletes, and little is known about the potential short-term and long-term neurologic sequelae.To determine whether cumulative impact exposure is associated with oculomotor functioning in motorsport drivers from the INDYCAR professional open-wheel automobile racing series.This is a longitudinal retrospective cohort study conducted across 3 racing seasons (2017-2019). Statistical analyses were conducted in November 2021. Data were retrieved from a secondary care setting associated with the INDYCAR series. INDYCAR series drivers who participated in 3 professional level racing seasons and were involved in at least 1 contact incident (ie, crash) in 2 of the 3 seasons were included in the study.Cumulative acceleration and deceleration forces and total contact incidents (ie, crashes) measured via accident data recorder third generation chassis and ear accelerometers.Postseries oculomotor performance, including predictive saccades, vergence smooth pursuit, and optokinetic nystagmus, was measured annually with a head-mounted, clinical eye tracking system (Neurolign Dx 100).Thirteen drivers (mean [SD] age, 29.36 [7.82] years; all men) sustained median resultant acceleration forces of 38.15 g (observed range, 12.01-93.05 g; 95% CI, 30.62-65.81 g) across 81 crashes. A 2-way multivariate analysis of variance did not reveal a statistically significant association between ear and chassis average resultant g forces, total number of contact incidents, and racing season assessed (F9,12 = 0.955; P = .54; Wilks Λ = 0.44).In this cohort study of professional drivers from the INDYCAR series, there were no statistically significant associations among cumulative impact exposure, racing season assessed, and oculomotor performance. Longitudinal studies across racing seasons using multidimensional examination modalities (eg, neurocognitive testing, advanced imaging, biomarkers, and physical examination) are critical to understand potential neurological and neurobehavioral sequelae and long-term consequences of cumulative impact exposure.
Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation Among Patients at Risk of Aspiration
Authors: Hugo Carvalho, Alain Kalmar, Sarah Saxena
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Screening for Latent Tuberculosis Infection in Adults
Authors: Daniel E. Jonas, Sean R. Riley, Lindsey C. Lee, Cory P. Coffey, Shu-Hua Wang, Gary N. Asher, Anne M. Berry, Niketa Williams, Casey Balio, Christiane E. Voisin, Leila C. Kahwati
Journal: JAMA (2023)

Importance Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality. Objective To review the evidence on benefits and harms of screening for and treatment of LTBI in adults to inform the US Preventive Services Task Force (USPSTF). Data Sources PubMed/MEDLINE, Cochrane Library, and trial registries through December 3, 2021; references; experts; literature surveillance through January 20, 2023. Study Selection English-language studies of LTBI screening, LTBI treatment, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of LTBI screening and treatment for public health surveillance or disease management were excluded. Data Extraction and Synthesis Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when a sufficient number of similar studies were available. Main Outcomes and Measures Screening test accuracy; development of active tuberculosis disease, transmission, quality of life, mortality, and harms. Results A total of 113 publications were included (112 studies; N = 69 009). No studies directly evaluated the benefits and harms of screening. Pooled estimates for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI, 0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial found a relative risk (RR) for progression to active tuberculosis at 5 years of 0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI, 2.03-10.39]; number needed to harm, 279). A previously published meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339). Conclusions and Relevance No studies directly evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs were moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduced the risk of progression to active tuberculosis. Isoniazid was associated with higher rates of hepatotoxicity than placebo or rifampin.
CIB2 Is a Novel Endogenous Repressor of Atrial Remodeling
Authors: Yihui Wang, Jizheng Wang, Ling Shi, Xiuyu Chen, Desheng Li, Chen Cui, Kai Yang, Minjie Lu, Jinhua Huang, Lei Zhang, Fei Li, Jinxi Wang, Biyi Chen, Bin Wang, Duane D. Hall, Zhenwei Pan, Jiang Hong, Long-Sheng Song, Lei Song, Shihua Zhao
Journal: Circulation (2023)

Background: Atrial fibrillation (AF) is a highly prevalent condition that can cause or exacerbate heart failure, is an important risk factor for stroke, and is associated with pronounced morbidity and death. Genes uniquely expressed in the atria are known to be essential for maintaining atrial structure and function. Atrial tissue remodeling contributes to arrhythmia recurrence and maintenance. However, the mechanism underlying atrial remodeling remains poorly understood. This study was designed to investigate whether other uncharacterized atrial specific genes play important roles in atrial physiology and arrhythmogenesis. Methods: RNA-sequencing analysis was used to identify atrial myocyte specific and angiotensin II–responsive genes. Genetically modified, cardiomyocyte-specific mouse models (knockout and overexpression) were generated. In vivo and in vitro electrophysiological, histology, and biochemical analyses were performed to determine the consequences of CIB2 (calcium and integrin binding family member 2 protein) gain and loss of function in the atrium. Results: Using RNA-sequencing analysis, we identified CIB2 as an atrial-enriched protein that is significantly downregulated in the left atria of patients with AF and mouse models of AF from angiotensin II infusion or pressure overload. Using cardiomyocyte-specific C ib2 knockout ( Cib2 -/ - ) and atrial myocyte–specific Cib2 -overexpressing mouse models, we found that loss of C ib2 enhances AF occurrence, prolongs AF duration, and correlates with a significant increase in atrial fibrosis under stress. Conversely, Cib2 overexpression mitigates AF occurrence and atrial fibrosis triggered by angiotensin II stress. Mechanistically, we revealed that CIB2 competes with and inhibits CIB1-mediated calcineurin activation, thereby negating stress-induced structural remodeling and AF. Conclusions: Our data suggest that CIB2 represents a novel endogenous and atrial-enriched regulator that protects against atrial remodeling and AF under stress conditions. Therefore, CIB2 may represent a new potential target for treating AF.
Ophthalmic Technician Working in Central Pennsylvania
Authors: Anushka Shah
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal